Search

Jan P Vandenbroucke,1– 3 Henrik Toft Sørensen,1,4 David H Rehkopf,5 Jaimie L Gradus,6 Johan P Mackenbach,7 M Maria Glymour,8 Sandro Galea,9 Victor W Henderson1,10 1Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark; 2Leiden University, Leiden, Netherlands; 3London School of Hygiene & Tropical Medicine, London, UK; 4Aarhus University Hospital, Aarhus, Denmark; 5Stanford Center for Population Health Sciences, Stanford University, CA, USA; 6Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA; 7Department of Public Health, Erasmus University Rotterdam, Rotterdam, Holland; 8Department of Epidemiology, Boston University School of Public Health, Boston University, Boston, MA, USA; 9School of Public Health, Boston University, Boston, MA, USA; 10Departments of Epidemiology & Population Health and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USAAbstract: This paper is a summary of key presentations from a workshop in Iceland on May 3– 4, 2023 arranged by Aarhus University and with participation of the below-mentioned scientists.Below you will find the key messages from the presentations made by:Professor Jan Vandenbroucke, Department of Clinical Epidemiology, Aarhus University, Emeritus Professor, Leiden University; Honorary Professor, London School of Hygiene & Tropical Medicine, UKProfessor, Chair Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, DenmarkProfessor David H. Rehkopf, Director, the Stanford Center for Population Health Sciences, Stanford University, CA., USProfessor Jaimie Gradus, Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, USProfessor Johan Mackenbach, Emeritus Professor, Department of Public Health, Erasmus University Rotterdam, HollandProfessor, Chair M Maria Glymour, Department of Epidemiology, Boston University School of Public Health, Boston

Importance Traumatic events have been associated with elevated risks of psychiatric disorders, while the contributions of familial factors to these associations remain less clear.Objective To determine the contribution of familial factors to long-term incidence trajectories of psychiatric disorders following potentially traumatic events.Design, Setting, and Participants This cohort study evaluated 3 separate cohorts of individuals residing in Sweden who were free of previous diagnosed psychiatric disorders when first exposed to assault (n = 49 957), injury (n = 555 314), or bereavement (n = 321 263) from January 1987 to December 2013, together with their unexposed full siblings, and 10 age-, sex-, and birthplace-matched unexposed individuals (per exposed individual). Cohorts were created from the Swedish Total Population Register linked to health and population registers. Data were analyzed from March 2022 to April 2023.Exposures Potentially traumatic events, including various types of assault, injuries, and bereavement (death of a child or of a spouse or partner), were ascertained from the Swedish national registers.Main Outcomes and Measures Incident psychiatric disorders were ascertained from the Swedish Patient Register. Flexible parametric and Cox models were used to estimate associations of potentially traumatic events with incident psychiatric disorders after multivariable adjustment.Results The median (IQR) age at exposure to assault, injury, and bereavement was 22 (18-31), 19 (8-40), and 60 (51-68) years, respectively. During a median (IQR) follow-up of 4.9 (2.2-8.2), 9.1 (4.1-15.6), and 8.1 (3.4-14.8) years, the incidence rates of any psychiatric disorder were 38.1, 13.9, and 9.0 per 1000 person-years for the exposed groups of the 3 cohorts, respectively. Elevated risk of any psychiatric disorder was observed during the first year after exposure to any assault (hazard ratio [HR], 4.55; 95% CI, 4.34-4.77), injury (HR, 3.31; 95% CI,3.23-3.38), or bereavement

IMPORTANCE: Traumatic events have been associated with elevated risks of psychiatric disorders, while the contributions of familial factors to these associations remain less clear. OBJECTIVE: To determine the contribution of familial factors to long-term incidence trajectories of psychiatric disorders following potentially traumatic events. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated 3 separate cohorts of individuals residing in Sweden who were free of previous diagnosed psychiatric disorders when first exposed to assault (n = 49 957), injury (n = 555 314), or bereavement (n = 321 263) from January 1987 to December 2013, together with their unexposed full siblings, and 10 age-, sex-, and birthplace-matched unexposed individuals (per exposed individual). Cohorts were created from the Swedish Total Population Register linked to health and population registers. Data were analyzed from March 2022 to April 2023. EXPOSURES: Potentially traumatic events, including various types of assault, injuries, and bereavement (death of a child or of a spouse or partner), were ascertained from the Swedish national registers. MAIN OUTCOMES AND MEASURES: Incident psychiatric disorders were ascertained from the Swedish Patient Register. Flexible parametric and Cox models were used to estimate associations of potentially traumatic events with incident psychiatric disorders after multivariable adjustment. RESULTS: The median (IQR) age at exposure to assault, injury, and bereavement was 22 (18-31), 19 (8-40), and 60 (51-68) years, respectively. During a median (IQR) follow-up of 4.9 (2.2-8.2), 9.1 (4.1-15.6), and 8.1 (3.4-14.8) years, the incidence rates of any psychiatric disorder were 38.1, 13.9, and 9.0 per 1000 person-years for the exposed groups of the 3 cohorts, respectively. Elevated risk of any psychiatric disorder was observed during the first year after exposure to any assault (hazard ratio [HR], 4.55; 95% CI, 4.34-4.77), injury (HR, 3.31; 95% CI,3.23-3.38), or, This work was supported by EU Horizon 2020 Research and Innovation Action grant 847776 (Valdimarsdóttir), Grant of Excellence, Icelandic Research Fund grant 163362-051 (Valdimarsdóttir), European Research Council Consolidator grant 726413 (Valdimarsdóttir), the Project for Disciplines of Excellence, West China Hospital, Sichuan University grant ZYYC21005 (Song), the Outstanding Clinical Discipline Project of Shanghai Pudong grant PWYgy2021-02, and the Fundamental Research Funds for the Central Universities (Shen).

This paper is a summary of key presentations from a workshop in Iceland on May 3– 4, 2023 arranged by Aarhus University and with participation of the below-mentioned scientists. Below you will find the key messages from the presentations made by:Professor Jan Vandenbroucke, Department of Clinical Epidemiology, Aarhus University, Emeritus Professor, Leiden University; Honorary Professor, London School of Hygiene & Tropical Medicine, UKProfessor, Chair Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, DenmarkProfessor David H. Rehkopf, Director, the Stanford Center for Population Health Sciences, Stanford University, CA., USProfessor Jaimie Gradus, Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, USProfessor Johan Mackenbach, Emeritus Professor, Department of Public Health, Erasmus University Rotterdam, HollandProfessor, Chair M Maria Glymour, Department of Epidemiology, Boston University School of Public Health, Boston University, Boston, Massachusetts, USProfessor, Dean Sandro Galea, School of Public Health, Boston University, Boston, Massachusetts, USProfessor Victor W. Henderson, Departments of Epidemiology & Population Health and of Neurology & Neurological Sciences, Stanford University, Stanford, CA, US; Department of Clinical Epidemiology, Aarhus University, Aarhus, DK

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and experiences of psychological trauma have been associated with subsequent CVD onset. Identifying key pathways connecting trauma with CVD has the potential to inform more targeted screening and intervention efforts to offset elevated cardiovascular risk. In this narrative review, we summarize the evidence for key psychological and biological mechanisms linking experiences of trauma with CVD risk. Additionally, we describe various methodologies for measuring these mechanisms in an effort to inform future research related to potential pathways. With regard to mechanisms involving posttraumatic psychopathology, the vast majority of research on psychological distress after trauma and CVD has focused on posttraumatic stress disorder (PTSD), even though posttraumatic psychopathology can manifest in other ways as well. Substantial evidence suggests that PTSD predicts the onset of a range of cardiovascular outcomes in trauma-exposed men and women, yet more research is needed to better understand posttraumatic psychopathology more comprehensively and how it may relate to CVD. Further, dysregulation of numerous biological systems may occur after trauma and in the presence of posttraumatic psychopathology; these processes of immune system dysregulation and elevated inflammation, oxidative stress, mitochondrial dysfunction, renin-angiotensin system dysregulation, and accelerated biological aging may all contribute to subsequent cardiovascular risk, although more research on these pathways in the context of traumatic stress is needed. Given that many of these mechanisms are closely intertwined, future research using a systems biology approach may prove fruitful for elucidating how processes unfold to contribute to CVD after trauma.

Military personnel deployed to war zones are at increased risk of mental health problems such as posttraumatic stress disorder (PTSD) or depression. Early pre- or post-deployment identification of those at highest risk of such problems is crucial to target intervention to those in need. However, sufficiently accurate models predicting objectively assessed mental health outcomes have not been put forward. In a sample consisting of all Danish military personnel who deployed to war zones for the first (N = 27,594), second (N = 11,083) and third (N = 5,161) time between 1992 and 2013, we apply neural networks to predict psychiatric diagnoses or use of psychotropic medicine in the years following deployment. Models are based on pre-deployment registry data alone or on pre-deployment registry data in combination with post-deployment questionnaire data on deployment experiences or early post-deployment reactions. Further, we identified the most central predictors of importance for the first, second, and third deployment. Models based on pre-deployment registry data alone had lower accuracy (AUCs ranging from 0.61 (third deployment) to 0.67 (first deployment)) than models including pre- and post-deployment data (AUCs ranging from 0.70 (third deployment) to 0.74 (first deployment)). Age at deployment, deployment year and previous physical trauma were important across deployments. Post-deployment predictors varied across deployments but included deployment exposures as well as early post-deployment symptoms. The results suggest that neural network models combining pre- and early post-deployment data can be utilized for screening tools that identify individuals at risk of severe mental health problems in the years following military deployment.

BackgroundSubstance use disorders (SUD) elevate the risk for COVID-19 hospitalization, but studies are inconsistent on the relationship of SUD to COVID-19 mortality.MethodsVeterans Health Administration (VHA) patients treated in 2019 and evaluated in 2020 for COVID-19 (n=5,556,315), of whom 62,303 (1.1%) tested positive for COVID-19 (COVID-19+). Outcomes were COVID-19+ by 11/01/20, hospitalization, ICU admission, or death within 60 days of a positive test. Main predictors were any ICD-10-CM SUDs, with substance-specific SUDs (cannabis, cocaine, opioid, stimulant, sedative) explored individually. Logistic regression produced unadjusted and covariate-adjusted odds ratios (OR; aOR).ResultsAmong COVID-19+ patients, 19.25% were hospitalized, 7.71% admitted to ICU, and 5.84% died. In unadjusted models, any SUD and all substance-specific SUDs except cannabis use disorder were associated with COVID-19+(ORs=1.06-1.85); adjusted models produced similar results. Any SUD and all substance-specific SUDs were associated with hospitalization (aORs: 1.24-1.91). Any SUD, cocaine and opioid disorder were associated with ICU admission in unadjusted but not adjusted models. Any SUD, cannabis, cocaine, and stimulant disorders were inversely associated with mortality in unadjusted models (OR=0.27-0.46). After adjustment, associations with mortality were no longer significant. In ad hoc analyses, adjusted odds of mortality were lower among the 49.9% of COVID-19+ patients with SUD who had SUD treatment in 2019, but not among those without such treatment.ConclusionsIn VHA patients, SUDs are associated with COVID-19 hospitalization but not COVID-19 mortality. SUD treatment may provide closer monitoring of care, ensuring that these patients received needed medical attention, enabling them to ultimately survive serious illness.

BackgroundSubstance use disorders (SUD) elevate the risk for COVID-19 hospitalization, but studies are inconsistent on the relationship of SUD to COVID-19 mortality.MethodsVeterans Health Administration (VHA) patients treated in 2019 and evaluated in 2020 for COVID-19 (n=5,556,315), of whom 62,303 (1.1%) tested positive for COVID-19 (COVID-19+). Outcomes were COVID-19+ by 11/01/20, hospitalization, ICU admission, or death within 60 days of a positive test. Main predictors were any ICD-10-CM SUDs, with substance-specific SUDs (cannabis, cocaine, opioid, stimulant, sedative) explored individually. Logistic regression produced unadjusted and covariate-adjusted odds ratios (OR; aOR).ResultsAmong COVID-19+ patients, 19.25% were hospitalized, 7.71% admitted to ICU, and 5.84% died. In unadjusted models, any SUD and all substance-specific SUDs except cannabis use disorder were associated with COVID-19+(ORs=1.06-1.85); adjusted models produced similar results. Any SUD and all substance-specific SUDs were associated with hospitalization (aORs: 1.24-1.91). Any SUD, cocaine and opioid disorder were associated with ICU admission in unadjusted but not adjusted models. Any SUD, cannabis, cocaine, and stimulant disorders were inversely associated with mortality in unadjusted models (OR=0.27-0.46). After adjustment, associations with mortality were no longer significant. In ad hoc analyses, adjusted odds of mortality were lower among the 49.9% of COVID-19+ patients with SUD who had SUD treatment in 2019, but not among those without such treatment.ConclusionsIn VHA patients, SUDs are associated with COVID-19 hospitalization but not COVID-19 mortality. SUD treatment may provide closer monitoring of care, ensuring that these patients received needed medical attention, enabling them to ultimately survive serious illness.

ObjectiveIn the United States, adult cannabis use has increased over time, but less information is available on time trends in cannabis use disorder. The authors used Veterans Health Administration (VHA) data to examine change over time in cannabis use disorder diagnoses among veterans, an important population subgroup, and whether such trends differ by age group (<35 years, 35-64 years, ≥65 years), sex, or race/ethnicity.MethodsVHA electronic health records from 2005 to 2019 (range of Ns per year, 4,403,027-5,797,240) were used to identify the percentage of VHA patients seen each year with a cannabis use disorder diagnosis (ICD-9-CM, January 1, 2005-September 30, 2015; ICD-10-CM, October 1, 2015-December 31, 2019). Trends in cannabis use disorder diagnoses were examined by age and by race/ethnicity and sex within age groups. Given the transition in ICD coding, differences in trends were tested within two periods: 2005-2014 (ICD-9-CM) and 2016-2019 (ICD-10-CM).ResultsIn 2005, the percentages of VHA patients diagnosed with cannabis use disorder in the <35, 35-64, and ≥65 year age groups were 1.70%, 1.59%, and 0.03%, respectively; by 2019, the percentages had increased to 4.84%, 2.86%, and 0.74%, respectively. Although the prevalence of cannabis use disorder was consistently higher among males than females, between 2016 and 2019, the prevalence increased more among females than males in the <35 year group. Black patients had a consistently higher prevalence of cannabis use disorder than other racial/ethnic groups, and increases were greater among Black than White patients in the <35 year group in both periods.ConclusionsSince 2005, diagnoses of cannabis use disorder have increased substantially among VHA patients, as they have in the general population and other patient populations. Possible explanations warranting investigation include decreasing perception of risk, changing laws, increasing cannabis potency, stressors related to growing socioeconomic ine

ObjectiveThe Department of Veterans Affairs' (VA) electronic health records (EHR) offer a rich source of big data to study medical and health care questions, but patient eligibility and preferences may limit generalizability of findings. We therefore examined the representativeness of VA veterans by comparing veterans using VA healthcare services to those who do not.MethodsWe analyzed data on 3051 veteran participants age ≥ 18 years in the 2019 National Health Interview Survey. Weighted logistic regression was used to model participant characteristics, health conditions, pain, and self-reported health by past year VA healthcare use and generate predicted marginal prevalences, which were used to calculate Cohen's d of group differences in absolute risk by past-year VA healthcare use.ResultsAmong veterans, 30.4% had past-year VA healthcare use. Veterans with lower income and members of racial/ethnic minority groups were more likely to report past-year VA healthcare use. Health conditions overrepresented in past-year VA healthcare users included chronic medical conditions (80.6% vs. 69.4%, d = 0.36), pain (78.9% vs. 65.9%; d = 0.35), mental distress (11.6% vs. 5.9%; d = 0.47), anxiety (10.8% vs. 4.1%; d = 0.67), and fair/poor self-reported health (27.9% vs. 18.0%; d = 0.40).ConclusionsHeterogeneity in veteran sociodemographic and health characteristics was observed by past-year VA healthcare use. Researchers working with VA EHR data should consider how the patient selection process may relate to the exposures and outcomes under study. Statistical reweighting may be needed to generalize risk estimates from the VA EHR data to the overall veteran population.

There is an association between stress and dementia. However, less is known about dementia among persons with varied stress responses and sex differences in these associations. We used this population-based cohort study to examine dementia among persons with a range of clinician-diagnosed stress disorders, as well as the interaction between stress disorders and sex in predicting dementia, in Denmark from 1995 to 2011. This study included Danes aged 40 years or older with a stress disorder diagnosis (n = 47,047) and a matched comparison cohort (n = 232,141) without a stress disorder diagnosis with data from 1995 through 2011. Diagnoses were culled from national registries. We used Cox proportional hazards regression to estimate associations between stress disorders and dementia. Risk of dementia was higher for persons with stress disorders than for persons without such diagnosis; adjusted hazard ratios ranged from 1.6 to 2.8. There was evidence of an interaction between sex and stress disorders in predicting dementia, with a higher rate of dementia among men with stress disorders except posttraumatic stress disorder, for which women had a higher rate. Results support existing evidence of an association between stress and dementia. This study contributes novel information regarding dementia risk across a range of stress responses, and interactions between stress disorders and sex.

BackgroundPosttraumatic stress disorder is a well-documented risk factor for cardiovascular disease. Whether non-specific stress-related psychopathology also increases risk is less well known.MethodsIn a cohort of adult Danish-born residents of Denmark with an incident diagnosis of unspecified reaction to severe stress ("unspecified stress reaction") between 1995 and 2011 (N = 24,534), we assessed incidence of seven arterial and venous cardiovascular events/conditions between 1996 and 2013. We calculated standardized incidence ratios (SIRs) comparing incidence of each outcome among the cohort to expected incidence based on sex-, age-, and calendar-time-specific national rates. We conducted stratified analyses by demographic characteristics, comorbidities, and length of follow-up time.ResultsIncidence over the study period ranged from 1.1% for provoked VTE to 5.7% for stroke, adjusting for competing risk of death. Unspecified stress reaction was associated with all outcomes (SIRs ranging from 1.3, 95% confidence interval (CI): 1.1-1.4 for atrial fibrillation/flutter to 1.9, 95% CI: 1.7-2.2 for unprovoked VTE and 1.9, 95% CI: 1.6-2.3 for provoked VTE). Associations persisted, but were attenuated, when restricting to persons without alcohol use disorder and to persons without physical health comorbidities.LimitationsUnspecified stress reaction has less precise criteria than other stress-related diagnoses, and we could not adjust for some potential confounders.ConclusionsOur results augment literature on stress disorders and cardiovascular disease by highlighting the additional importance of unspecified stress disorders. Further research on this diagnostic category, which may represent subsyndromal psychopathology, is warranted. These findings support considering persons with non-specific stress-related psychopathology in treatment and tertiary prevention activities.

Objective: Mental health problems (MHP) are a relatively common consequence of deployment to war zones. Early identification of those at risk of post-deployment MHP would improve prevention efforts. However, screening instruments based on linear models have not been successful. Machine learning (ML) has shown promise for providing the methodological frame for better prognostic models. Methods: The study population was all Danish military personnel deployed for the first time between January 1, 1992 and December 31, 2013. From extensive registry data, 21 pre- or at-deployment predictors comprising early adversity, social, clinical and demographic variables were used to predict psychiatric contacts (psychiatric diagnosis and/or use of psychotropic medicine) occurring within 6.5 years after homecoming. Four supervised ML methods (penalized logistic regression, random forests, support vector machines and gradient boosting machines) were compared in ability to classify those with high risk of post-deployment MHP and those without. Results: Of 27594 subjects, 2175 (8%) had a psychiatric contact. All four ML methods applied had performances well above chance (Area under the Receiver-operating Curve 0.62-0.68). Positive predictive value for the best model was 0.16. A range of pre-deployment factors were found to be predictive of post-deployment psychiatric contacts. Conclusions: ML methods can be useful in early identification of soldiers with high risk of MPH in the years following their first deployment. However, performances were modest and positive predictive values were low, limiting the applicability of the models for pre-deployment screening. Future studies should include neurobiological data and deployment experiences to increase accuracy of the models.

OBJECTIVE:There is some evidence that posttraumatic stress disorder (PTSD) is associated with increased risk of infections, and it is unknown whether adjustment disorder is as well. We assessed the association between adjustment disorder and subsequent infections, and assessed additive interaction with sex. METHODS:The study population included a nationwide cohort of all Danish-born residents of Denmark diagnosed with adjustment disorder between 1995 and 2011, and an age- and sex-matched general population comparison cohort. We compared rates of infections requiring inpatient or outpatient hospitalization in the two cohorts. We fit Cox proportional hazards models to compute adjusted hazard ratios (aHR) for the associations between adjustment disorder and 32 types of infections, and calculated interaction contrasts to assess interaction between adjustment disorder and sex. RESULTS:Adjustment disorder was associated with increased rates of infections overall (n = 19,838 infections, aHR = 1.8, 95% confidence interval = 1.8. 1.9), and increased rates of each individual infection type (aHRs for 30 infections ranged from 1.5 to 2.3), adjusting for baseline psychiatric and somatic comorbidities and marital status. For many infection types (e.g., skin infections, pneumonia), interaction contrasts indicated rate differences were greater among men than women, while for two (urinary tract infections and sexually transmitted infections), rate differences were greater for women. CONCLUSIONS:These findings are consistent with studies examining the relationship between psychological stress and infections, and between PTSD and infections. They may be explained by a combination of the triggering of unhealthy behaviors as well as immune responses to stress.

OBJECTIVE:There is some evidence that posttraumatic stress disorder (PTSD) is associated with increased risk of infections, and it is unknown whether adjustment disorder is as well. We assessed the association between adjustment disorder and subsequent infections, and assessed additive interaction with sex. METHODS:The study population included a nationwide cohort of all Danish-born residents of Denmark diagnosed with adjustment disorder between 1995 and 2011, and an age- and sex-matched general population comparison cohort. We compared rates of infections requiring inpatient or outpatient hospitalization in the two cohorts. We fit Cox proportional hazards models to compute adjusted hazard ratios (aHR) for the associations between adjustment disorder and 32 types of infections, and calculated interaction contrasts to assess interaction between adjustment disorder and sex. RESULTS:Adjustment disorder was associated with increased rates of infections overall (n = 19,838 infections, aHR = 1.8, 95% confidence interval = 1.8. 1.9), and increased rates of each individual infection type (aHRs for 30 infections ranged from 1.5 to 2.3), adjusting for baseline psychiatric and somatic comorbidities and marital status. For many infection types (e.g., skin infections, pneumonia), interaction contrasts indicated rate differences were greater among men than women, while for two (urinary tract infections and sexually transmitted infections), rate differences were greater for women. CONCLUSIONS:These findings are consistent with studies examining the relationship between psychological stress and infections, and between PTSD and infections. They may be explained by a combination of the triggering of unhealthy behaviors as well as immune responses to stress.

Jaimie L Gradus,1 Erzsébet Horváth-Puhó,2 Tammy Jiang,1 Anthony J Rosellini,3 Timothy L Lash,4 Henrik Toft Sørensen2 1Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; 2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 3Center for Anxiety and Related Disorders, Boston University, Boston, MA, USA; 4Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USACorrespondence: Jaimie L GradusDepartment of Epidemiology, Boston University School of Public Health, Boston, MA, USAEmail jgradus@bu.eduComplications following organ transplant – such as complex medical regimens involving adherence to lifelong immunosuppressant medications, adverse effects, infection, and rejection of the transplanted organ – may increase the risk of stress and mental disorders.1 Only one population-based study has examined the association between organ transplant and suicide, and found that the suicide rate among liver transplant recipients was five times that of the Nordic general population between the years 2000 and 2010.2 In this study, we examined associations between heart, lung, kidney, and liver transplants and suicide and non-fatal suicide attempts in the population of Denmark.

The association between stress and cancer incidence has been studied for more than seven decades. Despite plausible biological mechanisms and evidence from laboratory studies, findings from clinical research are conflicting. The objective of this study was to examine the association between PTSD and various cancer outcomes. This nation-wide cohort study included all Danish-born residents of Denmark from 1995 to 2011. The exposure was PTSD diagnoses (n = 4131). The main outcomes were cancer diagnoses including: (1) all malignant neoplasms; (2) hematologic malignancies; (3) immune-related cancers; (4) smoking- and alcohol-related cancers; (5) cancers at all other sites. Standardized incidence ratios (SIR) were calculated. Null associations were found between PTSD and nearly all cancer diagnoses examined, both overall [SIR for all cancers = 1.0, 95 % confidence interval (CI) = 0.88, 1.2] and in analyses stratified by gender, age, substance abuse history and time since PTSD diagnosis. This study is the most comprehensive examination to date of PTSD as a predictor of many cancer types. Our data show no evidence of an association between PTSD and cancer in this nationwide cohort.

Yael I Nillni,1,2 Amelia K Wesselink,3 Elizabeth E Hatch,3 Ellen M Mikkelsen,4 Jaimie L Gradus,1–3 Kenneth J Rothman,3,5 Lauren A Wise3 1Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA; 2National Center for PTSD, Women’s Health Sciences Division at VA Boston Healthcare System, Boston, MA, USA; 3Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; 4Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark; 5RTI Health Solutions, Research Triangle, NC, USA Purpose: To examine the influence of depressive symptoms, perceived stress, and psychotropic medication use on prospectively assessed menstrual cycle regularity and length.Participants and methods: Data were obtained from Pregnancy Study Online, a prospective cohort study of pregnancy planners from North America. At baseline, women reported information on demographics, anthropometrics, lifestyle, and medical history, including their use of psychotropic medications. They also completed the Major Depression Inventory and the Perceived Stress Scale. Every 8 weeks for up to 12 months or until conception, women completed follow-up questionnaires to assess changes in psychotropic medication use, perceived stress, and menstrual cycle characteristics (ie, cycle regularity and length). Women who completed at least one follow-up questionnaire from 2013 to 2018 (n=3,346) were included in the primary analyses. A total of 5,439 women were included in secondary analyses utilizing baseline data only. Primary analyses estimated prevalence ratios (PR) and 95% CIs using log-binomial regression models.Results: Women with severe depressive symptoms at baseline, regardless of psychotropic medication use, had an 80% greater prevalence of irregular cycles during follow-up than women with no or low depressive symptoms (PR =1.80, 95% CI =1.48–2.19). Perceived stress was also associated with the prevalence of irregular cycles during

Jaimie L Gradus1–4 1National Center for PTSD, VA Boston Healthcare System, 2Department of Psychiatry, Boston University School of Medicine, 3Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Abstract: Given the ubiquity of traumatic events, it is not surprising that posttraumatic stress disorder (PTSD) – a common diagnosis following one of these experiences – is characterized as conferring a large burden for individuals and society. Although there is recognition of the importance of PTSD diagnoses throughout psychiatry, the literature on other diagnoses one may receive following a stressful or traumatic event is scant. This review summarizes the literature on stress disorders (classified according to the International Classification of Diseases, 10th Edition [ICD-10]), including acute stress reaction, PTSD, adjustment disorder and unspecified stress reactions. This review focuses on the literature related to common psychiatric and somatic consequences of these disorders. The prevalence and incidence of each disorder are described. A review of epidemiologic studies on comorbid mental health conditions, including depression, anxiety and substance abuse, is included, as well as a review of epidemiologic studies on somatic outcomes, including cancer, cardiovascular disease and gastrointestinal disorders. Finally, the current literature on all-cause mortality and suicide following stress disorder diagnoses is reviewed. Stress disorders are a critical public health issue with potentially deleterious outcomes that have a significant impact on those living with these disorders, the health care system and society. It is only through an awareness of the impact of stress disorders that appropriate resources can be allocated to prevention and treatment. Future research should expand the work done to date beyond the examination of

Elisabeth Svensson,1 Timothy L Lash,1,2 Patricia A Resick,3 Jens Georg Hansen,1 Jaimie L Gradus4–61Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; 3Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; 4National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA; 5Department of Psychiatry, 6Department of Epidemiology, Boston University, Boston, MA, USAAims: To assess the validity of reaction to severe stress and adjustment disorder diagnoses registered in the Danish Psychiatric Central Research Register (DPCRR), to examine the documentation of stressful and traumatic events in the medical records, and to investigate the occurrence of stress diagnoses among persons not registered in the DPCRR.Methods: Among 101,633 patients diagnosed with International Classification of Diseases, 10th Edition (ICD-10) F43 diagnoses between 1995 and 2011, we selected 50 patients from two hospitals (100 total), comprising one above and one below median age for each diagnosis for five time periods, and reviewed their medical records. We calculated the positive predictive value, comparing registration in the DPCRR with the original medical records, and captured data on stressful life events. Two general practitioners were queried about 50 patients without a stress diagnosis in the DPCRR, regarding whether they had ever received a stress diagnosis.Results: The positive predictive value was 58% for acute stress reaction, 83% for posttraumatic stress disorder, 94% for adjustment disorder, 71% for other reactions to severe stress, and 68% for reaction to severe stress, unspecified. In 80% of the records, a stressful or traumatic event was noted. Of 100 patients without an F43 diagnosis in the DPCRR, seven had a stress diagnosis.Conclusion: The DPCRR represents a valid and comprehe

Charlotte Gjørup Pedersen,1 Jaimie L Gradus,2 Søren Paaske Johnsen,3 Jan Mainz1,41Department South, Aalborg Psychiatric Hospital, Aalborg, Denmark; 2VA Boston Healthcare System, National Center for PTSD and Boston University, Boston, MA, USA; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Health Services Research, University of Southern Denmark, Odense, DenmarkBackground: Improvement of quality of care for psychiatric patients is a key objective of health care systems worldwide. Consequently, there is an increasing interest in documenting quality of care; however, little is known about the validity of the available data on psychiatric care.Objective: To assess the validity of process of care data recorded in the Danish National Indicator Project (DNIP), a national population-based registry containing quality of care data of patients diagnosed with schizophrenia in Denmark.Methods: A random sample of 1% of patients with schizophrenia registered in the DNIP between 2004 and 2009 (111 inpatient and 85 outpatient) was identified for validation. Medical records for these patients, which were used as the gold standard, were retrieved and reviewed for information on the processes of care received. Agreement between the data in the DNIP and the medical records were assessed by computing sensitivity, specificity, and positive and negative predictive values.Results: The agreement between the recorded processes of care in the DNIP and in the medical records varied substantially across the individual process of care variables. However, a collection of the processes of care demonstrated a high agreement (80% or more) between data in the DNIP and the medical records, according to all examined aspects of data validity (sensitivity, specificity, and positive and negative predictive values). The medical records contained varying levels of missing information regarding the processes of care, from 1% for antipsyc

Jaimie L Gradus1,2, Ping Qin3, Alisa K Lincoln4, Matthew Miller5, Elizabeth Lawler6, Timothy L Lash2,71National Center for PTSD VA Boston Healthcare System, Boston, MA, USA; 2Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; 3National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; 4Health Sciences and Sociology Departments, Northeastern University, Boston, MA, USA; 5Department of Health Policy and Management, Harvard University School of Public Health, Boston, MA, USA; 6Department of Medicine, Harvard University, Boston, MA, USA; 7Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, DenmarkAbstract: Adjustment disorder is a diagnosis given following a significant psychosocial stressor from which an individual has difficulty recovering. The individual’s reaction to this event must exceed what would be observed among similar people experiencing the same stressor. Adjustment disorder is associated with suicidal ideation and suicide attempt. However the association between adjustment disorder and completed suicide has yet to be examined. The current study is a population-based case control study examining this association in the population of Denmark aged 15 to 90 years. All suicides in Denmark from 1994 to 2006 were included, resulting in 9,612 cases. For each case, up to 30 controls were matched on gender, exact date of birth, and calendar time, yielding 199,306 controls. Adjustment disorder diagnosis was found in 7.6% of suicide cases and 0.52% of controls. Conditional logistic regression analyses revealed that those diagnosed with adjustment disorder had 12 times the rate of suicide as those without an adjustment disorder diagnosis, after controlling for history of depression diagnosis, marital status, income, and the matched factors.Keywords: adjustment disorder, suicide, case-control study